Citrate Synthase: Difference between revisions

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[[Image:2cts polyview.jpg|450px|left|thumb| Citrate synthase 'closed form', [[2cts]]]]

==The Structure and Mechanism of Citrate Synthase==

Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate. Although it is a mitochondrial enzyme (in fact, it is often used as a quantitative enzyme marker for intact mitochondria), it is encoded by nuclear DNA, not mitochondrial <ref>"Citrate Synthase -." Wikipedia, the Free Encyclopedia. Web. 22 Mar. 2010. <http://en.wikipedia.org/wiki/Citrate_synthase></ref>. The standard free energy change (ΔG°’) for the citrate synthase reaction is

-31.5kJ/mol <ref name="voet">Voet, Donald, Judith G. Voet, and Charlotte W. Pratt. Fundamentals of Biochemistry: Life at the Molecular Level. Hoboken, NJ: Wiley, 2008.</ref>. This negative free energy value means that citrate synthase is likely to function far from equilibrium under physiological conditions, and is thus a rate-determining enzyme in the citric acid cycle.

'''Structure:''' Biologically, citrate synthase exists as a

<scene name='Daniel_Eddelman_Sandbox_2/Cts_open_monomer/2'>homodimer</scene> of a single amino acid chain <scene name='Daniel_Eddelman_Sandbox_2/Cts_open_monomer/1'>monomer</scene>. Each identical subunit consists of a large and a small domain, and is comprised almost entirely of α helices (making it an all α protein). In its free enzyme state, citrate synthase exists in “open” form, with its two domains forming a cleft containing the substrate (oxaloacetate) binding site (PDB: [[1cts]]) <ref>PMID:7120407</ref>. When oxaloacetate binds, the smaller domain undergoes an 18° rotation, sealing the oxaloacetate binding site and resulting in the <scene name='Daniel_Eddelman_Sandbox_2/Closed_homodimer/1'>closed conformation of the homodimer</scene> (PDB: [[2cts]])<ref>PMID:7308213</ref>. The dramatic conformational change is best illustrated via <scene name='User:Wayne_Decatur/1cts_to_2cts_(citrate_synthase)_morph_methods/1ctsto2ctsmorph/5'>a morph between the "open" and "closed" states</scene>. <nowiki>[</nowiki>Be patient; it may take longer than half a minute for the morph to load. <nowiki>]</nowiki> The conformational change not only prevents solvent from reaching the bound substrate, but also generates the acetyl-CoA binding site. This presence of “open” and “closed” forms results in citrate synthase having Ordered Sequential kinetic behavior <ref name="voet" />.<br>

<scene name='Daniel_Eddelman_Sandbox_2/Cts_open_monomer/2'>homodimer</scene> of a single amino acid chain <scene name='Daniel_Eddelman_Sandbox_2/Cts_open_monomer/1'>monomer</scene>. Each identical subunit consists of a large and a small domain, and is comprised almost entirely of α helices (making it an all α protein). In its free enzyme state, citrate synthase exists in <scene name='Daniel_Eddelman_Sandbox_2/Cts_open_monomer/2'>an “open” form of the homodimer</scene>, with its two domains forming a cleft containing the substrate (oxaloacetate) binding site (PDB: [[1cts]]) <ref>PMID:7120407</ref>. When oxaloacetate binds, the smaller domain undergoes an 18° rotation, sealing the oxaloacetate binding site and resulting in the <scene name='Daniel_Eddelman_Sandbox_2/Closed_homodimer/1'>closed conformation of the homodimer</scene> (PDB: [[2cts]])<ref>PMID:7308213</ref>. The dramatic conformational change is best illustrated via <scene name='User:Wayne_Decatur/1cts_to_2cts_(citrate_synthase)_morph_methods/1ctsto2ctsmorph/5'>a morph between the "open" and "closed" states</scene>. <nowiki>[</nowiki>Be patient; it may take longer than half a minute for the morph to load. <nowiki>]</nowiki> The conformational change not only prevents solvent from reaching the bound substrate, but also generates the acetyl-CoA binding site. This presence of “open” and “closed” forms results in citrate synthase having Ordered Sequential kinetic behavior <ref name="voet" />.<br>

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Citrate Synthase: Difference between revisions

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 [[Image:2cts polyview.jpg|450px|left|thumb| Citrate synthase 'closed form', [[2cts]]]]
 ==The Structure and Mechanism of Citrate Synthase==
-<Structure load='1cts' size='400' frame='true' align='right' scene='Daniel_Eddelman_Sandbox_2/Cts_open_monomer/2' caption='Citrate Synthase' />
+<Structure load='1cts' size='480' frame='true' align='right' scene='Daniel_Eddelman_Sandbox_2/Cts_open_monomer/2' caption='Citrate Synthase' />
 Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate.  Although it is a mitochondrial enzyme (in fact, it is often used as a quantitative enzyme marker for intact mitochondria), it is encoded by nuclear DNA, not mitochondrial <ref>"Citrate Synthase -." Wikipedia, the Free Encyclopedia. Web. 22 Mar. 2010. <http://en.wikipedia.org/wiki/Citrate_synthase></ref>. The standard free energy change (ΔG°’) for the citrate synthase reaction is
 -31.5kJ/mol <ref name="voet">Voet, Donald, Judith G. Voet, and Charlotte W. Pratt. Fundamentals of Biochemistry: Life at the Molecular Level. Hoboken, NJ: Wiley, 2008.</ref>. This negative free energy value means that citrate synthase is likely to function far from equilibrium under physiological conditions, and is thus a rate-determining enzyme in the citric acid cycle.
 '''Structure:''' Biologically, citrate synthase exists as a
-<scene name='Daniel_Eddelman_Sandbox_2/Cts_open_monomer/2'>homodimer</scene>  of a single amino acid chain <scene name='Daniel_Eddelman_Sandbox_2/Cts_open_monomer/1'>monomer</scene>. Each identical subunit consists of a large and a small domain, and is comprised almost entirely of α helices (making it an all α protein).  In its free enzyme state, citrate synthase exists in “open” form, with its two domains forming a cleft containing the substrate (oxaloacetate) binding site (PDB: [[1cts]]) <ref>PMID:7120407</ref>.  When oxaloacetate binds, the smaller domain undergoes an 18° rotation, sealing the oxaloacetate binding site and resulting in the <scene name='Daniel_Eddelman_Sandbox_2/Closed_homodimer/1'>closed conformation of the homodimer</scene> (PDB: [[2cts]])<ref>PMID:7308213</ref>.   The dramatic conformational change is best illustrated via <scene name='User:Wayne_Decatur/1cts_to_2cts_(citrate_synthase)_morph_methods/1ctsto2ctsmorph/5'>a morph between the "open" and "closed" states</scene>. <nowiki>[</nowiki>Be patient; it may take longer than half a minute for the morph to load. <nowiki>]</nowiki> The conformational change not only prevents solvent from reaching the bound substrate, but also generates the acetyl-CoA binding site.  This presence of “open” and “closed” forms results in citrate synthase having Ordered Sequential kinetic behavior <ref name="voet" />.<br>
+<scene name='Daniel_Eddelman_Sandbox_2/Cts_open_monomer/2'>homodimer</scene> of a single amino acid chain <scene name='Daniel_Eddelman_Sandbox_2/Cts_open_monomer/1'>monomer</scene>. Each identical subunit consists of a large and a small domain, and is comprised almost entirely of α helices (making it an all α protein).  In its free enzyme state, citrate synthase exists in <scene name='Daniel_Eddelman_Sandbox_2/Cts_open_monomer/2'>an “open” form of the homodimer</scene>, with its two domains forming a cleft containing the substrate (oxaloacetate) binding site (PDB: [[1cts]]) <ref>PMID:7120407</ref>.  When oxaloacetate binds, the smaller domain undergoes an 18° rotation, sealing the oxaloacetate binding site and resulting in the <scene name='Daniel_Eddelman_Sandbox_2/Closed_homodimer/1'>closed conformation of the homodimer</scene> (PDB: [[2cts]])<ref>PMID:7308213</ref>.   The dramatic conformational change is best illustrated via <scene name='User:Wayne_Decatur/1cts_to_2cts_(citrate_synthase)_morph_methods/1ctsto2ctsmorph/5'>a morph between the "open" and "closed" states</scene>. <nowiki>[</nowiki>Be patient; it may take longer than half a minute for the morph to load. <nowiki>]</nowiki> The conformational change not only prevents solvent from reaching the bound substrate, but also generates the acetyl-CoA binding site.  This presence of “open” and “closed” forms results in citrate synthase having Ordered Sequential kinetic behavior <ref name="voet" />.<br>
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